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Groves, A.K. etal. Repair of demyelinated lesions by transplantation of purified O-2A progenitor cells. Nature 362, 453- 455

Department of Veterinary Medicine, University of Cambridge, Cambridge, England, United Kingdom
Nature (Impact Factor: 42.35). 05/1993; 362(6419):453-5. DOI: 10.1038/362453a0
Source: PubMed

ABSTRACT The transplantation of well defined populations of precursor cells offers a means of repairing damaged tissue and of delivering therapeutic compounds to sites of injury or degeneration. For example, a functional immune system can be reconstituted by transplantation of purified haematopoietic stem cells, and transplanted skeletal myoblasts and keratinocytes can participate in the formation of normal tissue in host animals. Cell transplantation in the central nervous system (CNS) has been proposed as a means of correcting neuronal dysfunction in diseases associated with neuronal loss; it might also rectify glial cell dysfunction, with transplanted oligodendrocyte precursor cells eventually allowing repair of demyelinating damage in the CNS. Here we use co-operating growth factors to expand purified populations of oligodendrocyte type-2 astrocyte (O-2A) progenitor cells for several weeks in vitro. When injected into demyelinating lesions in spinal cords of adult rats, created in such a way as to preclude host-mediated remyelination, these expanded populations are capable of producing extensive remyelination. In addition, transplantation of O-2A progenitor cells genetically modified to express the bacterial beta-galactosidase gene gives rise to beta-galactosidase-positive oligodendrocytes which remyelinate demyelinated axons within the lesion. These results offer a viable strategy for the manipulation of neural precursor cells which is compatible with attempts to repair damaged CNS tissue by precursor transplantation.

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    • "Glial cell death via apoptosis, particularly loss of myelinating OLGs, may result in consequent axonal demyelination (Jensen et al. 1999; Tamura et al. 2005; Warden et al. 2001). In support this hypothesis, remyelination of the spinal cord axons via cell transplantation (Akiyama et al. 2002; Groves et al. 1993; Keirstead et al. 2005) or transplants combined with cAMP elevation or neurotrophic factors (Cao et al. 2005; Pearse et al. 2004) have been shown to improve functional recovery in SCI rodents significantly. In addition, RhoA might negatively regulate myelin formation in the CNS because RhoA activation by Lingo1, a protein present in OLGs, appears to suppress myelination of CNS axons (Mi et al. 2005; Mi et al. 2009). "
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    • "Still, one must be cautious in interpretation of these results until a functional assessment of the transplanted cells is performed. Nevertheless, several other studies demonstrate that the ability of OPCs to engraft and myelinate decreases over time in culture (Feltri et al. 1992; Groves et al. 1993; Trotter et al. 1993). Culturing oligodendrocyte-lineage cells may make them less likely to myelinate when transplanted, as they lose their proliferative ability and differentiate in vitro (Richter and Roskams 2008). "
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    • "These results are consistent with previous studies. Bi-potential OPCs from neonatal optical nerve or brain differentiate along OL lineages without astrocyte commitment after transplantation into the adult demyelinated (Groves et al., 1993) or contused (Lee et al., 2005) spinal cord. Since astrocyte differentiation from grafted NSCs enhances the plasticity of pain fibers and promotes allodynia after SCI (Hofstetter et al., 2005), lack of astrocyte differentiation and concomitant allodynia plus its greatest potential for OL differentiation may make adult OPCs an ideal candidate for cell grafts to OL replacement and remyelination after SCI. "
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